Elsevier

Molecular Metabolism

Volume 6, Issue 2, February 2017, Pages 219-225
Molecular Metabolism

Brief Communication
Carnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation

https://doi.org/10.1016/j.molmet.2016.12.008Get rights and content
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Highlights

  • Role of CrAT in macrophage inflammation was tested in vivo.

  • Myeloid CrAT does not regulate inflammation during HFD-induced obesity.

  • Fasting-induced metabolic stress is not regulated by myeloid CrAT expression.

  • CrAT expression in myeloid cells does not regulate LPS-induced acute endotoxemia.

  • Mitochondrial acetyl-CoA efflux via CrAT does not regulate macrophage inflammation.

Abstract

Objective

Fatty acid oxidation in macrophages is thought to regulate inflammatory status and insulin-sensitivity. An important unanswered question in this field is whether carnitine acetyl-transferase (CrAT) that regulates fatty acid oxidation and mitochondrial acetyl-CoA balance is required to integrate nutrient stress sensing to inflammatory response in macrophages.

Methods

Mice with myeloid lineage-specific Crat deletion were subjected to several metabolic stressors, including high-fat diet-induced obesity, fasting, and LPS-induced endotoxemia. Their metabolic homeostasis was compared to that of Crat-sufficient littermate controls. Inflammatory potential of Crat-deficient and Crat-sufficient macrophages were measured both in vitro and in vivo.

Results

Our studies revealed that ablation of CrAT in myeloid lineage cells did not impact glucose homeostasis, insulin-action, adipose tissue leukocytosis, and inflammation when animals were confronted with a variety of metabolic stressors, including high-fat diet, fasting, or LPS-induced acute endotoxemia.

Conclusions

These findings demonstrate that unlike muscle cells, substrate switch mechanisms that control macrophage energy metabolism and mitochondrial short-chain acyl-CoA pools during nutrient stress are controlled by pathways that are not solely reliant on CrAT.

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Keywords

Macrophage
Adipose tissue
Inflammation
Carnitine acyltransferase

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